Technical Abstract:
While there is antigenic cross reactivity between bovine viral diarrhea virus genotype 1 (BVDV1) and bovine viral diarrhea virus genotype 2 (BVDV2) strains, cross neutralizing titers are typically a log or more higher between BVD viruses within the same genotype compared to viruses from different genotypes. This observation has prompted vaccine manufacturers in North America to produce vaccines that contained antigens from both BVDV1 and BVDV2 strains. As of January 2004, as least five major biologics companies were marketing modified live and/or killed vaccines containing both BVDV1 and BVDV2 strains. Under experimental conditions there new vaccines offer improved protection against type 2 strains, however field data is still insufficient to assess their efficacy in practice. Safety concerns have been raised regarding use of multiple BVDV strains in the same modified live vaccine. Specifically there are questions regarding the possibility of recombination between cytopathic BVDV vaccine strains contained in the same modified live vaccine. The concern was that a recombination between the two vaccine strains could give rise to a noncytopathic virus that would pose a danger for fetal infection. Researchers have reported recombination between vaccine strains and field strains. However, these recombinations were not between two cytopathic vaccine strains, but between a cytopathic vaccine strain and a non cytopathic strain. The recombined viruses were isolated from persistently infected (PI) animals that succumbed to mucosal disease (MD) following vaccination. It was theorized that a recombination between the cytopathic virus in the vaccine and the noncytopathic virus present in the persistently infected animal gave rise to a third virus that was cytopathic. This "new" cytopathic virus was identical to the persistent virus with the exception of an insertion. The sequence of the insertions was always identical to sequences found in the vaccine virus used to vaccinate the PI animal. To date, there have been no observations, either in vitro or in vivo, of recombination between cytopathic viruses giving rise to noncytopathic viruses. In addition there have been no reports of increased reproductive disease within herds under vaccine programs using combination type 1 and 2 modified live vaccines. Further, the recognition of subgenotypes of BVDV1 and BVDV2 may lead to future changes in U.S. vaccines. Recently, surveys of prevalence of BVDV 1 subgenotypes in North America have led to suggestions that protection may be improved by inclusion of strains from BVDV subgenotype 1a and BVDV subgenotype 1b in vaccines in addition to BVDV2 strains. However, the cost to benefit ration of this proposal is currently a matter of debate.